Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants.

We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (Pinteraction=0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy.

Increasing the accuracy of peanut allergy diagnosis by using Ara h 2.

BACKGROUND: Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitization but does not reliably predict allergy. Ara h 2 is the dominant peanut allergen detected in 90% to 100% of patients with peanut allergy and could help improve diagnosis. OBJECTIVES: We sought to determine whether Ara h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC). METHODS: Infants from the population-based HealthNuts study underwent skin prick tests to determine peanut sensitization and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random sample of 200 infants (100 with peanut allergy and 100 with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified by using fluorescence enzyme immunoassay. RESULTS: By using the previously published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut sIgE. We report that when using a combined approach of plasma sIgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two thirds. CONCLUSION: Ara h 2 plasma sIgE test levels provide higher diagnostic accuracy than whole peanut plasma sIgE levels and could be considered a new diagnostic tool to distinguish peanut allergy from peanut tolerance, which might reduce the need for an OFC.

An update on epidemiology of anaphylaxis in children and adults.

PURPOSE OF REVIEW: The purpose of the present review is to describe the epidemiology of food-induced, medication-induced, drug-induced, and insect sting-induced anaphylaxis; to summarize recent changes in the incidence of anaphylaxis internationally; and to discuss recent insights into potential risk factors for anaphylaxis. RECENT FINDINGS: Recent studies confirm that the incidence of anaphylaxis, particularly food-induced anaphylaxis, is increasing world-wide. The rise in anaphylaxis incidence appears most pronounced in children under the age of 5 years, which is also the age group most at risk of hospitalization for food-induced anaphylaxis. Identification of factors that may increase the risk of episodes of anaphylaxis remains an important research priority. Recently, two large cohort studies using data from electronic medical records confirmed that individuals with asthma are at higher risk of anaphylaxis and those with severe asthma have the highest risk of all. With respect to modifiable lifestyle factors, several studies have demonstrated a link between latitude and anaphylaxis, with areas with less year-round sunlight reporting a higher prevalence of food-induced anaphylaxis. SUMMARY: Reports of an increasing incidence of anaphylaxis internationally highlight the need for identification of modifiable risk factors for anaphylaxis. Emerging evidence suggests that low vitamin D levels may be associated with risk of anaphylaxis and food allergy; however, further studies are required to confirm this.

Childhood eczema and rhinitis predict atopic but not nonatopic adult asthma: a prospective cohort study over 4 decades.

BACKGROUND: The evidence on whether the atopic march observed in childhood (ie, the progression from eczema to allergic rhinitis and asthma) extends to adulthood is sparse, and there is no evidence on whether the progression leads to a specific phenotype of asthma. OBJECTIVE: We sought to assess whether childhood eczema and rhinitis are risk factors for specific phenotypes of adult asthma. METHODS: Participants of the Tasmanian Longitudinal Health Study recruited in 1968 (age range, 6.0-7.0 years) were followed up at age 44 years. The risk of current atopic or nonatopic asthma in middle age characterized by sensitization to aeroallergens given childhood eczema, rhinitis, or both was calculated by using multinomial logistic regression. RESULTS: No association was found between childhood eczema or rhinitis and nonatopic adult asthma. In contrast, childhood eczema and rhinitis in combination predicted both new-onset atopic asthma by middle age (adjusted multinomial odds ratio [aMOR], 6.3; 95% CI, 1.7-23.2) and the persistence of childhood asthma to adult atopic asthma (aMOR, 11.7; 95% CI, 3.6-37.9). Participants with childhood eczema alone were at increased risk of new-onset atopic asthma (aMOR, 4.1; 95% CI, 1.9-8.8), whereas rhinitis alone predicted the persistence of childhood asthma to atopic asthma (aMOR, 2.7; 95% CI, 1.3-5.6). Of all asthma, 29.7% of persistent atopic asthma and 18.1% of new-onset atopic asthma could be attributed to having childhood eczema and rhinitis. CONCLUSION: Childhood eczema and rhinitis are strongly associated with the incidence and persistence of adult atopic asthma.

Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants.

BACKGROUND: Several indicators suggest that food allergy in infants is common and possibly increasing. Few studies have used oral food challenge to measure this phenomenon at the population level. OBJECTIVE: To measure the prevalence of common IgE-mediated childhood food allergies in a population-based sample of 12-month-old infants by using predetermined food challenge criteria to measure outcomes. METHODS: A sampling frame was used to select recruitment areas to attain a representative population base. Recruitment occurred at childhood immunization sessions in Melbourne, Australia. Infants underwent skin prick testing, and those with any sensitization (wheal size ≥ 1 mm) to 1 or more foods (raw egg, peanut, sesame, shellfish, or cow's milk) were invited to attend an allergy research clinic. Those who registered a wheal size ≥ 1 mm to raw egg, peanut, or sesame underwent oral food challenge. RESULTS: Amongst 2848 infants (73% participation rate), the prevalence of any sensitization to peanut was 8.9% (95% CI, 7.9-10.0); raw egg white, 16.5% (95% CI, 15.1-17.9); sesame, 2.5% (95% CI, 2.0-3.1); cow's milk, 5.6% (95% CI, 3.2-8.0); and shellfish, 0.9% (95% CI, 0.6-1.5). The prevalence of challenge-proven peanut allergy was 3.0% (95% CI, 2.4-3.8); raw egg allergy, 8.9% (95% CI, 7.8-10.0); and sesame allergy, 0.8% (95% CI, 0.5-1.1). Oral food challenges to cow's milk and shellfish were not performed. Of those with raw egg allergy, 80.3% could tolerate baked egg. CONCLUSION: More than 10% of 1-year-old infants had challenge-proven IgE-mediated food allergy to one of the common allergenic foods of infancy. The high prevalence of allergic disease in Australia requires further investigation and may be related to modifiable environmental factors.

Can early introduction of egg prevent egg allergy in infants? A population-based study.

BACKGROUND: Infant feeding guidelines have long recommended delaying introduction of solids and allergenic foods to prevent allergy in high-risk infants, despite a paucity of evidence. OBJECTIVE: We aimed to determine whether confirmed egg allergy in 12-month-old infants is associated with (1) duration of breast-feeding and (2) ages of introducing egg and solids. METHODS: In a population-based cross-sectional study (HealthNuts) parents reported on infant feeding and potential confounding factors before skin prick testing for egg white. Egg-sensitized infants were then offered an egg oral food challenge. Multiple logistic regression was used to investigate associations between diet and egg allergy adjusted for possible confounding factors. RESULTS: A total of 2589 infants (73% response) participated. Compared with introduction at 4 to 6 months, introducing egg into the diet later was associated with higher risks of egg allergy (adjusted odds ratios [ORs], 1.6 [95% CI, 1.0-2.6] and 3.4 [95% CI, 1.8-6.5] for introduction at 10-12 and after 12 months, respectively). These findings persisted even in children without risk factors (OR, 3.3 [95% CI, 1.1-9.9]; 10-12 months). At age 4 to 6 months, first exposure as cooked egg reduced the risk of egg allergy compared with first exposure as egg in baked goods (OR, 0.2 [95% CI, 0.06-0.71]). Duration of breast-feeding and age at introduction of solids were not associated with egg allergy. CONCLUSIONS: Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. Changes in infant feeding guidelines could have a significant effect on childhood egg allergy and possibly food allergy more generally.

Clinical aspects of pediatric food allergy and failed oral immune tolerance.

Food allergy seems to represent a new spectrum of disease that has elicited significant community concern and extended waiting lists for allergists and gastroenterologists alike. The apparent rise in prevalence of IgE-mediated food allergy (and associated risk of anaphylaxis) has been postulated to result from effects of a "modern lifestyle" but as yet clear environmental risk factors have not yet emerged. Family history seems to contribute to risk suggesting that gene-environment interactions will be important for identifying a subpopulation with increased susceptibility to any identified lifestyle effects. Non-IgE-mediated food allergy (including food-induced enteropathies and colitides, eosinophilic esophagitis, and Crohn's disease) with potentially similar environmental triggers resulting in diverse immune dysregulatory mechanisms. The evidence underpinning the putative rise in food allergy is discussed and potential mechanisms of disease explored. Clinical aspects of various food allergic conditions including non-IgE-mediated food allergy are outlined.